ArticleThe Journal of cell biology2002
A combination of three distinct trafficking signals mediates axonal targeting and presynaptic clustering of GAD65.
Article in The Journal of cell biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 73 citations in OpenAlex.
- Presynaptic Trafficking of Glutamate Decarboxylase Isoforms Is Dispensable for Basal GABAergic Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets.International journal of experimental pathology · 2022Article
- Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery.Frontiers in cellular neuroscience · 2022Review
- A sticky situation: regulation and function of protein palmitoylation with a spotlight on the axon and axon initial segment.Neuronal signaling · 2021Review
- Regulation of Dynamic Protein S-Acylation.Frontiers in molecular biosciences · 2021Review
- Heterogeneous GAD65 Expression in Subtypes of GABAergic Neurons Across Layers of the Cerebral Cortex and Hippocampus.Frontiers in behavioral neuroscience · 2021Article
- Spatial organization of palmitoyl acyl transferases governs substrate localization and function.Molecular membrane biology · 2019Review
- Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell.Nature metabolism · 2019Article
- Aberrant Accumulation of the Diabetes Autoantigen GAD65 in Golgi Membranes in Conditions of ER Stress and Autoimmunity.Diabetes · 2016Article
- GABA-Synthesizing Enzymes in Calbindin and Calretinin Neurons in Monkey Prefrontal Cortex.Cerebral cortex (New York, N.Y. : 1991) · 2016Article
- Compartmentalization of GABA synthesis by GAD67 differs between pancreatic beta cells and neurons.PloS one · 2015Article
- Article
- Rapid, activity-independent turnover of vesicular transmitter content at a mixed glycine/GABA synapse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Palmitoylation of MPP1 (membrane-palmitoylated protein 1)/p55 is crucial for lateral membrane organization in erythroid cells.The Journal of biological chemistry · 2012Article
- Palmitoylation and trafficking of GAD65 are impaired in a cellular model of Huntington's disease.The Biochemical journal · 2012Article
- Two distinct mechanisms target GAD67 to vesicular pathways and presynaptic clusters.The Journal of cell biology · 2010Article
- Role of the proteasome in excitotoxicity-induced cleavage of glutamic acid decarboxylase in cultured hippocampal neurons.PloS one · 2010Article
- Article
- Actin and microtubule-based cytoskeletal cues direct polarized targeting of proteins in neurons.Science signaling · 2009Review
- Palmitoyl protein thioesterase-1 deficiency impairs synaptic vesicle recycling at nerve terminals, contributing to neuropathology in humans and mice.The Journal of clinical investigation · 2008Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The signals involved in axonal trafficking and presynaptic clustering are poorly defined. Here we show that targeting of the gamma-aminobutyric acid-synthesizing enzyme glutamate decarboxylase 65 (GAD65) to presynaptic clusters is mediated by its palmitoylated 60-aa NH(2)-terminal domain and that this region can target other soluble proteins and their associated partners to presynaptic termini. A Golgi localization signal in aa 1-23 followed by a membrane anchoring signal upstream of the palmitoylation motif are required for this process and mediate targeting of GAD65 to the cytosolic leaflet of Golgi membranes, an obligatory first step in axonal sorting. Palmitoylation of a third trafficking signal downstream of the membrane anchoring signal is not required for Golgi targeting. However, palmitoylation of cysteines 30 and 45 is critical for post-Golgi trafficking of GAD65 to presynaptic sites and for its relative dendritic exclusion. Reduction of cellular cholesterol levels resulted in the inhibition of presynaptic clustering of palmitoylated GAD65, suggesting that the selective targeting of the protein to presynaptic termini is dependent on sorting to cholesterol-rich membrane microdomains. The palmitoylated NH(2)-terminal region of GAD65 is the first identified protein region that can target other proteins to presynaptic clusters.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.